Obesity is a serious disease with major medical complications that affects 33.4% of the American population. Obesity in the US increased by 30% from 1980 to 1990. The etiology of this rise in obesity is not clear. It seems improbable that changes in behavior over only one decade could be responsible. An overlooked possibility for the increase could be an infectious etiology. Five different viruses have been reported to cause obesity in animal models but until now have not been thought to play a role in human obesity. An avian adenovirus, SMAM-1, and a human adenovirus, AD-36, produce a syndrome of visceral obesity in chickens, with paradoxical decreased serum cholesterol and triglycerides. In two preliminary studies, 19% of obese humans had serum antibodies to SMAM-1 in Bombay, and 17% had antibodies to AD-36 in Wisconsin. Both sets of antibody positive humans had lower serum cholesterol and triglycerides than did antibody negative humans. None of 14 lean humans tested to date had antibodies to AD-36. This proposal will focus on the human virus, AD-36. The objectives of the protocol are to determine if AD-36 is specific among human adenoviruses in causing obesity, to determine if AD-36 produces obesity in other animal models, specifically in mammals, and to evaluate if AD-36 is an etiologic factor in producing obesity in humans. Specific and non-specific antibodies to AD-36 will be developed and used to screen the 50 known human adenoviruses for cross reactivity. Cross reacting viruses will be injected into animals to determine if the obesity syndrome is specific. The time course, pathophysiology, and etiology of obesity with AD-36 infection in animals will be evaluated. A large number of obese and lean human will be screened for the presence of antibodies to AD-36. Throat swabs and fecal samples will be taken from individuals who are positive for AD-36 antibodies in an attempt to grow wild type AD-36, and any AD-36 isolates from humans will be injected into animals to confirm that they cause the obesity syndrome. Serum, throat swabs, and fecal samples will be obtained from first degree family members of AD-36 antibody positive individuals for screening for AD-36. Collaborative arrangements have been made to screen other populations of well characterized obese individuals for the presence of AD-36 antibodies. If infection with one or more viruses is capable of producing obesity in humans, the implications for the public health of the United States and the world is enormous.